The rat posterior insular cortex has recently been shown to possess cardiac chronotropic organization and therefore may be involved in cortical mechanisms of sudden death. In order to assess the potential of this region for cardiac arrhythmogenicity, phasic microstimulation of tachycardia zones was undertaken in the urethane-anesthetized rat. The insular stimulus was triggered by the R wave of the electrocardiogram (ECG) and delayed so that resultant putative cardiac sympathetic nerve activity would be synchronous with the T wave of the ECG. This resulted in increasing degrees of heart block leading to escape rhythms, ventricular ectopics and ultimately death in asystole. Heart block was associated with elevated plasma norepinephrine levels and myocardial damage. Such effects have not been previously demonstrated for a cortical site. These data suggest that pathophysiological activation of the insular cortex by stroke, epileptic seizure, or under conditions of severe emotional stress could predispose to ECG changes, cardiac arrhythmias and sudden death.